Project Summary The purpose of this grant submission is the proposal of the University of Pennsylvania Health System patient care structure as a Specialized Clinical Centers (SCC - Hubs) of the Early Phase Pain Investigation Clinical Network (EPPIC-Net). EPPIC-Net will serve as the cornerstone of the NIH's Helping to End Addiction Long- term (HEAL) Partnership. EPPIC-Net will provide a robust and readily accessible infrastructure for the rapid implementation and performance of high-quality, comprehensive studies of patients with well-defined pain conditions, and the rapid design and performance of high-quality Phase 2 clinical trials to test promising novel therapeutics for pain. Using the Hospital of the University of Pennsylvania as a Hub and 6 additional centers that are part of the Penn Health system, studies will be conducted as designed by the expertise of the EPPIC network which intends to bring intense focus to relatively small numbers of patients with clinically well-defined pain conditions and high unmet therapeutic needs. Studies may be performed in either adult or pediatric populations. The Penn SCC expects to be testing novel, efficient study designs including adaptive and platform designs, validation studies of biomarkers, and biomarker-informed proof of principle or target engagement studies in phase 2 trials of interventions from academic and industry partners. The Penn site will assist the EPPIC-Net to make clinical, neuroimaging, biomarker, and preclinical data, as well as biosamples, available through public access data and biospecimen repositories. It is anticipated that EPPIC-Net will be able to run at least as five Phase 2 trials concurrently, in addition to deep clinical phenotyping and biomarker validation studies. The SCC will be expected to work collaboratively with the other SCC as well as the EPPIC-Net Clinical Coordinating Center (CCC) and Data Coordinating Center (DCC). The Penn-SCC will have ready access to patient populations with specific pain conditions and have expertise in their characterization. A Penn- SCC Hub will additionally provide scientific leadership and administrative oversight to its 6 satellite sites (?spokes?). The current proposal is for the establishment of the Penn-SCC Hub and spokes, and identification of potential populations but will not include funding for any of the clinical trials to be conducted. This will be negotiated later in a separate contract with the EPPIC Network and NIH. The diversity supplement to this trial will allow Kendall Smith, currently in his second year of the Doctoral of Nursing Practice -Nurse Anesthesia program (DNAP) to actively participate in the process of the development, conduct, and analysis of clinical trials to be developed in the EPPIC Network. He will bring his interest and experience with diversity issues in medical care to the overall process. He will also design and complete a study of patient response to pain treatment comparing subgroups including male vs female, and North American vs Western European populations, using data made available to him through his mentor, who is PI of the Penn EPPIC-Net Hub.